title: A single dose of lipopolysaccharide into mice with emphysema mimics human chronic obstructive pulmonary disease exacerbation as assessed by micro-computed tomography.
abstract: Chronic obstructive pulmonary disease (COPD), manifested as emphysema and chronic airway obstruction, can be exacerbated by bacterial and viral infections. Although the frequency of exacerbations increases as the disease progresses, the mechanisms underlying this phenomenon are largely unknown, and there is a need for a simple in vivo exacerbation model. In this study, we compared four groups of mice treated with PBS alone, elastase alone, LPS alone, and elastase plus LPS. A single intratracheal administration of LPS to mice with elastase-induced emphysema provoked infiltration of inflammatory cells, especially CD8(+) T cells, into alveolar spaces and increased matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and perforin production in bronchoalveolar lavage fluid at the acute inflammatory phase compared with the other groups. We also measured the percentage of low-attenuation area (LAA%) in the above mice using micro-computed X-ray tomography. The LAA% was the most sensitive parameter for quantitative assessments of emphysema among all the parameters evaluated. Using the parameter of LAA%, we found significantly more severe alveolar destruction in the group treated with elastase plus LPS compared with the other groups during long-term longitudinal observations. We built three-dimensional images of the emphysema and confirmed that the lungs of elastase plus LPS-treated mice contained larger emphysematous areas than mice treated with elastase alone. Although human exacerbation of COPD is clinically and pathologically complicated, this simple mouse model mimics human cases to some extent and will be useful for elucidating its mechanism and developing therapeutic strategies.
authors.affiliation: 1 Disease Glycomics Team and.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Fujinawa
authors.forename: Fumi
authors.initials: F
authors.lastname: Ota
authors.forename: Shiho
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Angata
authors.forename: Manabu
authors.initials: M
authors.lastname: Ueno
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Maeno
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.forename: Congxiao
authors.initials: C
authors.lastname: Gao
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Kozui
authors.initials: K
authors.lastname: Kida
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D021621:Imaging, Three-Dimensional; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000633:toxicity; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D008070:Lipopolysaccharides; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse